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The knock-down of overexpressed EZH2 and BMI-1 does not prevent osteosarcoma growth Sasaki, Hiromi ササキ, ヒロミ 佐々木, 裕美 Setoguchi, Takao セトグチ, タカオ 瀬戸口, 啓夫 Matsunoshita, Yukihiro マツノシタ, ユキヒロ 松野下, 幸弘 Gao, Hui Hirotsu, Masataka ヒロツ, マサタカ 廣津, 匡隆 Komiya, Setsuro コミヤ, セツロウ 小宮, 節郎 open access polycomb protein osteosarcoma EZH2 BMI-1 Polycomb group proteins control the transcriptional memory of cells by maintaining the stable silencing of specific sets of genes through chromatin modifications. Polycomb group protein complexes control gene repression through recruitment of histone deacetylase. This recruitment leads to trimethylation of Lys27 of histone H3 (H3K27). Histone H3K27 trimethylation is a property of stably silenced heterochromatin. EZH2 and BMI-1 are pivotal components of polycomb group protein complexes. Increased EZH2 levels have been found in several malignancies and reported as a molecular biomarker of poor prognosis. Similarly, BMI-1 has also been found to be associated with malignant transformation. In addition, inhibition of EZH2 or BMI-1 inhibits the growth of various types of malignancies. The expression of BMI-1 and EZH2 in human osteosarcoma has not been clearly determined. We examined the potential involvement of aberrant polycomb group protein expression in the pathogenesis of osteosarcoma. Real-time PCR revealed that expression of EZH2 in 143B, HOS, NOS-1 and Saos2 was increased compared to normal osteoblasts. BMI-1 was also up-regulated in 143B, HOS and NOS-1. Expression of EZH2 and BMI-1 were up-regulated in osteosarcoma patient biopsy specimens compared to normal bone. Immunohistochemical examinations showed that EZH2 and BMI-1 were up-regulated in osteosarcoma cells and that trimethylation of histone H3K27 was increased. We examined the effects of knock down of EZH2 and BMI-1 by shRNA. Unexpectedly, the knock-down of EZH2 and BMI-1 did not prevent osteosarcoma growth either in vitro or in vivo. Our findings suggest that EZH2 and BMI-1 may be tumorassociated antigens of osteosarcoma, but are not useful molecular targets of osteosarcoma treatment. Spandidos Publications 2010-03-01 eng journal article VoR http://hdl.handle.net/10232/19978 https://ir.kagoshima-u.ac.jp/records/2808 https://doi.org/10.3892/or_00000684 1021335X Oncology Reports 23 3 677 684 https://ir.kagoshima-u.ac.jp/record/2808/files/The knock-down of overexpressed EZH2 and BMI-1 does not prevent osteosarcoma growth.pdf application/pdf 367.4 kB 2016-10-27 2010-03-01